There is a plethora of known drugs sometimes used singly, but mostly in combination, for treating solid and blood tumors in humans. Chemotherapeutic approaches using small molecules such a vincristine, gemcitabine, 5-fluorouracil, and a litany of others (such as Gleevec®) which are used mostly in combination therapies, is widespread. In addition, biologicals such as Rituxan®, Erbitux™, and Herceptin® have also been used. With the exception of Herceptin®, and Gleevec® which targets an abnormal BCR-ABL protein found in patients with chronic myelogenous leukemia and a few others, these treatments are generally applied to individual patients based on guesswork rather than analysis. The heterogeneity of tumor types, even within a given organ such as breast or prostate, makes it difficult to ascertain in advance whether an individual patient's malignancy will, or will not, be responsive to any particular protocol. To applicants' knowledge, at least until recently, only the administration of Herceptin® was systematically based on the results of a companion diagnostic on an individual patient for an indication of whether (or not) the tumor will respond. More recently, other attempts to individualize treatment have been implemented, including chemosensitivity screening and tests for an individual target (e.g., KRAS mutations) which are used by some doctors. Estrogen receptor screening is often done routinely before administration of tamoxifen.
Studies have been done, however, with respect to tumor types in pools of many patient samples derived from a given organ or of cancers of a particular type to identify, in general, which metabolic or signal transduction/biological pathways are dysregulated in tumors of various types and which genes are over-expressed- or under-expressed. For example, studies of micro-RNA production patterns in ovarian cancer have been conducted by Dahiya, N., et al., PLoS ONE (2008) 18:e2436. Attempting to find such patterns on an individual basis has been limited to the recently reported sequencing of the entire genome of tumor cells from an individual patient at the cost of over $1 million, and as the patient had died before the project began, it too was not aimed at treatment of the patient herself. As the costs of sequencing have come down dramatically, a number of groups are conducting studies which attempt to sequence at least all of the open reading frames of genomes in cancer patients, comparing the sequences derived from tumor to those from normal tissue. The results of these studies are, at this point, unclear.
It would be extremely helpful to be able to formulate a treatment protocol for an individual patient based on the vulnerability of tumor cells in this patient to such a protocol as determined by the pathway-based irregularities which appear to be associated with the tumor. The present invention offers just such an opportunity.